STEM CELLS

Cover image for Vol. 34 Issue 6

Stem Cells Express (Accepted Articles - Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Edited By: Jan A. Nolta

Impact Factor: 5.902

ISI Journal Citation Reports © Ranking: 2015: 3/21 (CELL & TISSUE ENGINEERING); 8/70 (Hematology); 14/161 (Biotechnology & Applied Microbiology); 24/213 (Oncology); 34/187 (Cell Biology)

Online ISSN: 1549-4918

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  1. 1 - 38
  1. Embryonic Stem Cells/Induced Pluripotent Stem Cells

    1. Concise Review: Fate Determination of Stem Cells by Deubiquitinating Enzymes

      Arun Pandian Chandrasekaran, Bharathi Suresh, Hyongbum (Henry) Kim, Kye-Seong Kim and Suresh Ramakrishna

      Accepted manuscript online: 24 JUN 2016 10:35AM EST | DOI: 10.1002/stem.2446

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      Regulatory role of deubiquitinating enzymes in stem cell pluripotency and differentiation, cellular reprogramming and gametogenesis.

  2. Tissue-Specific Stem Cells

    1. Local CXCR4 Up-regulation in Injured Arterial Wall Contributes to Intimal Hyperplasia

      Xudong Shi, Lian-Wang Guo, Stephen Seedial, Toshio Takayama, Bowen Wang, Mengxue Zhang, Sarah R. Franco, Yi Si, Mirnal A Chaudhary, Bo Liu and K. Craig Kent

      Accepted manuscript online: 24 JUN 2016 10:35AM EST | DOI: 10.1002/stem.2442

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      A schematic model showing TGFβ/Smad3-stimulated CXCR4 expression in the vascular smooth muscle cell and its signaling activated by the SDF-1α ligand

  3. Embryonic Stem Cells/Induced Pluripotent Stem Cells

    1. CXCR4 Signaling Negatively Modulates the Bipotential State of Hemogenic Endothelial Cells Derived from Embryonic Stem Cells by Attenuating the Endothelial Potential

      Tanzir Ahmed, Kiyomi Tsuji-Tamura and Minetaro Ogawa

      Accepted manuscript online: 24 JUN 2016 10:35AM EST | DOI: 10.1002/stem.2441

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      ES cell-derived CD45- VE-cadherin+ CD41+ CXCR4+ cells represent a hemogenic endothelial cell (HEC) population. HECs encompass the differentiation programs for both the endothelial cell (EC) and hematopoietic cell (HC) lineages. A balance between these two programs provides an HEC with a bipotential state that allows the progeny of the cell to differentiate into both ECs and HCs. Fate of the bipotential HECs can be regulated by CXCL12/CXCR4 signaling, which suppresses the EC program independently of the hematopoietic fate.

  4. Cancer Stem Cells

    1. Positive Feedback Loop of OCT4 and c-JUN Expedites Cancer Stemness in Liver Cancer

      Kung-Kai Kuo, King-Teh Lee, Ker-Kong Chen, Ya-Han Yang, Ying-Chu Lin, Ming-Ho Tsai, Kenly Wuputra, Yen-Liang Lee, Chia-Chen Ku, Hiroyuki Miyoshi, Yukio Nakamura, Shigeo Saito, Chun-Chieh Wu, Chee-Yin Chai, Richard Eckner, Chen-Lung Steve Lin, Sophie S-W Wang, Deng-Chyang Wu, Chang-Shen Lin and Kazunari K. Yokoyama

      Accepted manuscript online: 24 JUN 2016 10:35AM EST | DOI: 10.1002/stem.2447

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      The OCT4/c-JUN positive feedback loop found in reprogrammed HepG2-derived cancer stem cell-like cells (rG2-DC-1C) sheds light on the tumorigenesis of liver cancer. 4F, Yamanaka 4 factors; iPS-like cells, induced pluripotent stemlike cells.

  5. Tissue-Specific Stem Cells

    1. Wnt Signaling Regulates Airway Epithelial Stem Cells in Adult Murine Submucosal Glands

      Thomas J. Lynch, Preston J. Anderson, Weiliang Xie, Adrianne K. Crooke, Xiaoming Liu, Scott R. Tyler, Meihui Luo, David M Kusner, Yulong Zhang, Traci Neff, Daniel C. Burnette, Katherine S. Walters, Michael J. Goodheart, Kalpaj R. Parekh and John F. Engelhardt

      Accepted manuscript online: 24 JUN 2016 10:35AM EST | DOI: 10.1002/stem.2443

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      Two distinct stem cell (SC) compartments in the mouse trachea include basal cells in the surface airway epithelium (SAE) and submucosal glands (SMGs). This research demonstrates that SCs from these two compartments have unique and overlapping properties that respond to dynamic changes in Wnt signaling following injury. Slowly cycling label retaining (LRC) SCs isolated from the SMGs had a greater proliferative capacity than SAE LRCs and glandular LRCs reside near Wnt-active tubules. Isolated glandular SCs had a greater regenerative capacity to reconstitute a denuded tracheal xenograft than SAE SCs, and only glandular SCs formed gland-like clones in xenografts and organoid cultures.

  6. Embryonic Stem Cells/Induced Pluripotent Stem Cells

    1. A Novel role for miR-1305 in Regulation of Pluripotency-Differentiation Balance, Cell Cycle and Apoptosis in Human Pluripotent Stem Cells

      Shibo Jin, Joseph Collin, Lili Zhu, David Montaner, Lyle Armstrong, Irina Neganova and Majlinda Lako

      Accepted manuscript online: 24 JUN 2016 03:31AM EST | DOI: 10.1002/stem.2444

  7. Tissue-Specific Stem Cells

    1. CXCR4+CD45- cells are niche forming for osteoclastogenesis via the SDF-1, CXCL7, and CX3CL1 signaling pathways in bone marrow

      Yoh Goto, Mineyoshi Aoyama, Takeo Sekiya, Hiroki Kakita, Yuko Waguri-Nagaya, Ken Miyazawa, Kiyofumi Asai and Shigemi Goto

      Accepted manuscript online: 24 JUN 2016 03:31AM EST | DOI: 10.1002/stem.2440

  8. Regenerative Medicine

    1. Glycoengineering of E-selectin ligands by intracellular versus extracellular fucosylation differentially affects osteotropism of human mesenchymal stem cells

      Brad Dykstra, Jungmin Lee, Luke J. Mortensen, Haixiao Yu, Zhengliang L. Wu, Charles P. Lin, Derrick J. Rossi and Robert Sackstein

      Accepted manuscript online: 22 JUN 2016 07:01PM EST | DOI: 10.1002/stem.2435

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      Two complimentary approaches were used to create E-selectin ligands on human mesenchymal stem cells (MSC) using fucosyltransferase VI (FTVI): extracellularly, by treating cells with purified FTVI enzyme, and intracellularly, by transfecting cells with FTVI-encoding modified mRNA. The extent to which the newly created E-selectin ligands could improve MSC homing to bone was tested using in vivo calvarial imaging. This three-dimensional reconstruction of a xenotransplanted mouse calvarium region shows bone (grey) and blood vessels (red), 24 hours after intravenously co-transplanting fucosylated MSCs (blue) and control MSCs (green). Both fucosylation approaches significantly increased homing of MSCs to the bone marrow, but intracellularly fucosylated (FUT6-mod) MSCs demonstrated increased extravasation into bone marrow parenchyma compared to their exofucosylated counterparts (FTVI-exo). The observed differential biologic effects of FTVI activity in these two contexts may yield new strategies for improving the efficacy of human MSCs in clinical applications. **p<0.01.

  9. Translational and Clinical Research

    1. Improved Mobilization of Exogenous Mesenchymal Stem Cells to Bone for Fracture Healing and Sex Difference

      Wei Yao, Evan Yu-An Lay, Alexander Kot, Ruiwu Liu, Hongliang Zhang, Haiyan Chen, Kit Lam and Nancy E. Lane

      Accepted manuscript online: 22 JUN 2016 07:01PM EST | DOI: 10.1002/stem.2433

  10. Regenerative Medicine

    1. HucMSC Exosome-Delivered 14-3-3ζ Orchestrates Self-control of the Wnt Response via Modulation of YAP during Cutaneous Regeneration

      Bin Zhang, Yinghong Shi, Aihua Gong, Zhaoji Pan, Hui Shi, Huan Yang, Hailong Fu, Yongmin Yan, Xu Zhang, Mei Wang, Wei Zhu, Hui Qian and Wenrong Xu

      Accepted manuscript online: 22 JUN 2016 07:01PM EST | DOI: 10.1002/stem.2432

  11. Embryonic Stem Cells/Induced Pluripotent Stem Cells

    1. Screening of Human cDNA Library Reveals Two Differentiation-related Genes, HHEX and HLX, as Promoters of Early Phase Reprogramming Toward Pluripotency

      Tatsuya Yamakawa, Yoshiko Sato, Yasuko Matsumura, Yukiko Kobayashi, Yoshifumi Kawamura, Naoki Goshima, Shinya Yamanaka and Keisuke Okita

      Accepted manuscript online: 22 JUN 2016 07:01PM EST | DOI: 10.1002/stem.2436

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      We used a new screening strategy that investigated the effects of genes from a human cDNA library on reprogramming and discovered two genes, HHEX and HLX, which may offer new understanding on the induction of pluripotency. This article is protected by copyright.

  12. Stem Cell Technology: Epigenetics, Genomics, Proteomics and Metabonomics

    1. Inhibition of lncRNA MIR31HG Promotes Osteogenic Differentiation of Human Adipose-Derived Stem Cells

      Chanyuan Jin, Lingfei Jia, Yiping Huang, Yunfei Zheng, Ning Du, Yunsong Liu and Yongsheng Zhou

      Accepted manuscript online: 22 JUN 2016 07:00PM EST | DOI: 10.1002/stem.2439

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      Schematic of the regulatory circuitry of MIR31HG and NF-κB. Under TNF-α and IL-17 stimulation, MIR31HG directly binds to IκBα and contributes to IκBα phosphorylation and NF-κB activation. The nuclear translocation of NF-κB in turn binds to MIR31HG promoter, upregulates its expression, and promotes its export to the cytoplasm where it exerts its function.

  13. Embryonic Stem Cells/Induced Pluripotent Stem Cells

    1. CREG1 Interacts with Sec8 to Promote Cardiomyogenic Differentiation and Cell-cell Adhesion

      Jie Liu, Yanmei Qi, Shaohua Li, Shu-Chan Hsu, Siavash Saadat, June Hsu, Saum A. Rahimi, Leonard Y. Lee, Chenghui Yan, Xiaoxiang Tian and Yanling Han

      Accepted manuscript online: 22 JUN 2016 07:00PM EST | DOI: 10.1002/stem.2434

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      Schematic model for a role of CREG1 in the formation of intercalated discs between cardiomyocytes. During cardiomyocyte differentiation from embryonic stem cells, CREG1 is upregulated and binds to Sec8 of the exocyst complex. The CREG1-exocyst interaction increases the delivery of N-cadherin from intracellular compartments, such as Golgi and recycling endosomes (ER), to the cell-cell adhesion sites, thereby promoting the formation of intercalated discs.

  14. Regenerative Medicine

    1. Generation of Induced Cardiospheres via Reprogramming of Skin Fibroblasts for Myocardial Regeneration

      Jian-Yong Xu, Yee-Ki Lee, Xinru Ran, Song-Yan Liao, Jiayin Yang, Ka-Wing Au, Wing-Hon Lai, Miguel A Esteban and Hung-Fat Tse

      Accepted manuscript online: 22 JUN 2016 07:00PM EST | DOI: 10.1002/stem.2438

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      TGF-β-expressing Mesenchymal Stem Cells Induce Local Tolerance in a Rat Liver Transplantation Model of Acute Rejection

      Jincao Tang, Renjie Yang, Ling Lv, Aihua Yao, Liyong Pu, Aihong Yin, Xiangcheng Li, Yue Yu, Scott L. Nyberg and Xuehao Wang

      Accepted manuscript online: 22 JUN 2016 07:00PM EST | DOI: 10.1002/stem.2437

  15. Embryonic Stem Cells/Induced Pluripotent Stem Cells

    1. Fibrinogen Induces RUNX2 Activity and Osteogenic Development from Human Pluripotent Stem Cells

      Fahad Kidwai, Jessica Edwards, Li Zou and Dan S. Kaufman

      Accepted manuscript online: 22 JUN 2016 06:55PM EST | DOI: 10.1002/stem.2427

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      Fibrinogen interaction with surface integrin (α9β1) mediates RUNX2 expression through SMAD1/5/8 signaling pathway and leads to osteogenic differentiation of human pluripotent stem cells.

    2. ErbB Receptor Tyrosine Kinase: A Molecular Switch between Cardiac and Neuroectoderm Specification in Human Pluripotent Stem Cells

      Chrishan J.A. Ramachandra, Ashish Mehta, Chong Hui Lua, Anuja Chitre, K.P. Myu Mai Ja and Winston Shim

      Accepted manuscript online: 21 JUN 2016 06:20AM EST | DOI: 10.1002/stem.2420

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      Convergence between EGFR/ErbB4 and Wnt3/Wnt11 signalling differentiates neuroectoderm and cardiomyocyte fate in human pluripotent stem cells (hPSC), highlighting cardiac mesoderm plasticity.

    3. Distinct Responses of stem Cells to Telomere Uncapping – a Potential Strategy to Improve the Safety Of Cell Therapy

      Chang Ching Liu, Dong Liang Ma, Ting-Dong Yan, XiuBo Fan, Zhiyong Poon, Lai-Fong Poon, Su-Ann Goh, Steve G. Rozen, William Ying Khee Hwang, Vinay Tergaonkar, Patrick Tan, Sujoy Ghosh, David M. Virshup, Eyleen L. K. Goh and Shang Li

      Accepted manuscript online: 14 JUN 2016 11:06AM EST | DOI: 10.1002/stem.2431

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      Inactivation of telomerase results in the functional uncoupling of the two unique properties of human pluripotent stem cells, namely self-renewal and pluripotency. This strategy allows us to create pluripotent stem cells with limited lifespan, which dramatically reduce the tumorigenicity of human pluripotent stem cells for clinical applications.

  16. Tissue-Specific Stem Cells

    1. Cytoarchitecture, Proliferative Activity and Neuroblast Migration in the Subventricular Zone and Lateral Ventricle Extension of the Adult Guinea Pig Brain

      Nery Jara, Manuel Cifuentes, Fernando Martínez, Katterine Salazar and Francisco Nualart

      Accepted manuscript online: 14 JUN 2016 10:56AM EST | DOI: 10.1002/stem.2430

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      Schematic summary of the cellular composition of the subventricular zone and lateral ventricle extension (LVE) of the adult guinea pig brain. In the adult guinea pig brain, a narrow ventricular cavity connects the SVZ with the OB, similar to the LVE previously described in the adult human brain. In the guinea pig brain, ependymal cells line the LV and also LVE; neuroblasts are located in the subependymal area, but mostly along the LVE; proliferating BrdU + cells are mainly found in the SVZ; however, they are also found in LVE. Astrocytes are co-distributed with neuroblasts in the SVZ and surround the neuroblasts in LVE. Finally, in the guinea pig brain the LVE has a reduced proliferative activity; however, it works as a continuous pathway for neuroblasts migration to the OB.

  17. Embryonic Stem Cells/Induced Pluripotent Stem Cells

    1. The Anterior-Posterior Patterning of Definitive Endoderm Generated from Human Embryonic Stem Cells Depends on the Differential Signaling of Retinoic Acid, Wnt- and BMP-Signaling

      Claudia Davenport, Ulf Diekmann, Insa Budde, Nora Detering and Ortwin Naujok

      Accepted manuscript online: 14 JUN 2016 10:51AM EST | DOI: 10.1002/stem.2428

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      Differentiation of pluripotent stem cells (PSC) via the definitive endoderm (DE) germ layer into the patterned primitive gut tube (PGT). The anterior-posterior axis of the PGT is controlled by differential signaling of Wnt/beta-catenin-, BMP-, FGF- and retinoic acid signaling. BMP inhibition (BMPi) and to a lesser Wnt/beta-catenin inhibition (WNTi) induce a foregut-like SOX2-positive state. Active Wnt/beta-catenin supported by BMPs, FGFs and all-trans retinoic acid (ATRA) induce a hindgut-like state. SOX2 is strongly expressed in PSCs, becomes down regulated during endoderm commitment, and reappears in the foregut domain upon A-P patterning, whereas CDX2 is expressed in the hindgut domain. ATRA is able to posteriorize the foregut.

  18. Cancer Stem Cells

    1. COX-2 Induces Breast Cancer Stem Cells via EP4/PI3K/AKT/NOTCH/WNT Axis

      Mousumi Majumder, Xiping Xin, Ling Liu, Elena Tutunea-Fatan, Mauricio Rodriguez-Torres, Krista Vincent, Lynne-Marie Postovit, David Hess and Peeyush K. Lala

      Accepted manuscript online: 14 JUN 2016 10:51AM EST | DOI: 10.1002/stem.2426

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      COX-2 upregulation or overexpression in human breast cancer cells increase EP4 expression, cell migration, invasion, proliferation, EMT and stem like cells (SLC) in human breast cancer. COX-2 overexpression activates NOTCH and WNT pathways and spheroids formation. COX-2 high cells promote tumor growth and metastassis in NOD/SCID mice. Serial transplantation of COX-2 high tumors promotes tumor growth and metastasis. Treatments with COX-2 inhibitor (I) or EP4 antagonist (A) or EP4 knock down (KD) in COX-2 high cells reduce above all phenotypes including lung metastasis. NOTCH and WNT inhibitors could abrogate COX-2 induced SLC functions. PI3K/AKT inhibition could reduce EP4 mediated SLC functions and NOTCH/WNT expression, establishing COX-2 induces SLC via EP4/PI3K/AKT/NOTCH/WNT pathway. In human breast tumor tissues COX-2 and EP4 expression increases with tumor progression, SLC marker colocalizes in COX-2 high cells and both COX-2/EP4 expression is associated with poor patient survival.

  19. Tissue-Specific Stem Cells

    1. Consecutive Alendronate Administration-Mediated Inhibition of Osteoclasts Improves Long-Term Engraftment Potential and Stress Resistance of HSCs

      Hyun-Jaung Sim, Sung-Ho Kook, Chi-Young Yun, Govinda Bhattarai, Eui-Sic Cho and Jeong-Chae Lee

      Accepted manuscript online: 14 JUN 2016 10:50AM EST | DOI: 10.1002/stem.2425

    2. Spla2-IIA Overexpression in Mice Epidermis Depletes Hair Follicle Stem Cells and Induce Differentiation Mediated through Enhanced JNK/C-Jun Activation

      Rahul M Sarate, Gopal L Chovatiya, Vagisha Ravi, Bharat Khade, Sanjay Gupta and Sanjeev K Waghmare

      Accepted manuscript online: 14 JUN 2016 10:47AM EST | DOI: 10.1002/stem.2418

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      Overexpression of sPLA2-IIA in mice epidermis leads to hyperplasia of both interfollicular epidermis and sebaceous gland, with enlarged size of the junctional zone and dermal papillae. In addition, loss of self-renewal in hair follicle stem cells was due to increased proliferation and differentiation, mediated through increased level of mitogenic signaling followed by enhanced expression of c-Jun, FosB and Nr4a1.

    3. Suppression of Neutrophil-Mediated Tissue Damage – A Novel Skill of Mesenchymal Stem Cells

      Dongsheng Jiang, Jana Muschhammer, Yu Qi, Andrea Kügler, Juliane C. de Vries, Mona Saffarzadeh, Anca Sindrilaru, Seppe Vander Beken, Meinhard Wlaschek, Mark A. Kluth, Christoph Ganss, Natasha Y. Frank, Markus H. Frank, Klaus T. Preissner and Karin Scharffetter-Kochanek

      Accepted manuscript online: 14 JUN 2016 10:47AM EST | DOI: 10.1002/stem.2417

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      Scheme of adaptive MSC responses to unrestrained neutrophil activation. Immune complexes inside and outside the vessel lead to unrestrained neutrophil activation with enhanced generation and release of O2 -. which can stimulate NET formation with expulsion of chromatin decorated with granules and highly concentrated MPO, NE and MMP-9, neutrophil death with spillage of their toxic cargo leading to tissue damage and tissue break down. Further damage to macromolecules occur by O2 -. and derivatives thereof like hydrogen peroxide (H2O2), peroxynitrate (ONNO.) and hydroxyl radicals (HO.). MSCs are able to mount an adaptive response to unrestrained neutrophil activation, with the release of O2 -. detoxifying extracellular SOD3 and ICAM-1/CD18 dependent engulfment of dying neutrophils thus preventing the spillage of their toxic cargo. By employing independent strategies MSCs effectively protect from tissue damage due to unrestrained neutrophil activation.

    4. Characterisation of the Epigenetic Changes During Human Gonadal Primordial Germ Cells Reprogramming

      C Eguizabal, L Herrera, L de Oñate, N Montserrat, P Hajkova and JC Izpisua Belmonte

      Accepted manuscript online: 14 JUN 2016 10:46AM EST | DOI: 10.1002/stem.2422

  20. Regenerative Medicine

    1. Ulk4 Regulates Neural Stem Cell Pool

      Min Liu, Zhenlong Guan, Qin Shen, Frances Flinter, Laura Domínguez, Joo Wook Ahn, David A Collier, Timothy O'Brien and Sanbing Shen

      Accepted manuscript online: 14 JUN 2016 10:46AM EST | DOI: 10.1002/stem.2423

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      Ulk4 regulates neural stem cell pool by tuning cell cycle and Wnt signaling pathway. Ulk4 is highly expressed in the G2/M phases and Ulk4 disruption alters expression levels of cell cycle-related molecules including Eml1, Pura and Apc. Ulk4 also modulates Wnt signaling pathway and Ulk4 gene deficiency decreases expression of Fzd, Apc and Lef1 which are known to positively influence neural stem cells, as well as elevated Wnt target of Vim which negatively regulates neurogenesis. Ulk4 is highly co-expressed in the SVZ of newborn mice with the proliferating marker Ki67 and Ulk4 mutation dramatically reduces the size of neural stem cell pool.

    2. Histone H3K9 Acetyltransferase PCAF is Essential for Osteogenic Differentiation through BMP Signaling and May Be Involved in Osteoporosis

      Ping Zhang, Yunsong Liu, Chanyuan Jin, Min Zhang, Longwei Lv, Xiao Zhang, Hao Liu and Yongsheng Zhou

      Accepted manuscript online: 14 JUN 2016 10:46AM EST | DOI: 10.1002/stem.2424

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      Osteogenic differentiation induced PCAF expression through SMADs; PCAF promoted activation of BMP2, BMP4, BMPR1B and RUNX2 by increasing H3K9ac, which led to osteogenic differentiation.

  21. Tissue-Specific Stem Cells

    1. Mesenchymal stem cells are recruited and activated into carcinoma-associated fibroblasts by prostate cancer microenvironment-derived TGF-β1

      Pedro Barcellos-de-Souza, Giuseppina Comito, Coral Pons-Segura, Maria Letizia Taddei, Valentina Gori, Valentina Becherucci, Franco Bambi, Francesca Margheri, Anna Laurenzana, Mario Del Rosso and Paola Chiarugi

      Accepted manuscript online: 14 JUN 2016 10:42AM EST | DOI: 10.1002/stem.2412

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      Prostate carcinoma microenvironment recruits and activates mesenchymal stem cells into CAF via TGF-β1.

      TGF-β 1 produced by prostate carcinoma (PCa) cells and tumor-associated fibroblasts and macrophages is important in bone marrow-derived mesenchymal stem cells (BM-MSC) recruitment to PCa site and further transdifferentiation to the carcinoma-associated fibroblast (CAF)-like phenotype. CAF-like MSC promote PCa cells invasiveness, perform vascular mimicry abilities and recruit monocytes, which can further polarize into M2-like macrophages.

  22. Cancer Stem Cells

    1. Immunomodulatory Factors Control the Fate of Melanoma Tumor Initiating Cells

      Alessandra Tuccitto, Marcella Tazzari, Valeria Beretta, Francesca Rini, Claudia Miranda, Angela Greco, Mario Santinami, Roberto Patuzzo, Barbara Vergani, Antonello Villa, Giacomo Manenti, Loredana Cleris, Daniele Giardiello, Malcolm Alison, Licia Rivoltini, Chiara Castelli and Michela Perego

      Accepted manuscript online: 14 JUN 2016 10:42AM EST | DOI: 10.1002/stem.2413

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      Melanoma is a heterogeneous tumor that shows a model of dynamic stemness (1). Melanoma cells temporally acquire tumorinitiating properties or switch from a status of tumorinitiating cells (TICs) to a more differentiated one depending on the tumor context (2). TICs produce IL10, while the differentiated cells release IL6. The selfproduced or exogenous IL10 sustains selfrenew and expansion of TICs (3) while IL6 promotes their differentiation (4). The functional heterogeneity of melanoma can be influenced by inflammatory and suppressive factors released also by cells constituting the tumor microenviroment. Our in vitro and in vivo experiments suggest that antiIL10 antibodies (αIL10 mAb) or antiIL6 receptor α (tocilizumab) might represent drugs for novel therapeutic strategies in melanoma patients (5).

  23. Embryonic Stem Cells/Induced Pluripotent Stem Cells

    1. Regulation of WNT Signaling by VSX2 during Optic Vesicle Patterning in Human Induced Pluripotent Stem Cells

      Elizabeth E Capowski, Lynda S Wright, Kun Liang, M. Joseph Phillips, Kyle Wallace, Anna Petelinsek, Anna Hagstrom, Isabel Pinilla, Katarzyna Borys, Jessica Lien, Jee Hong Min, Sunduz Keles, James A Thomson and David M Gamm

      Accepted manuscript online: 14 JUN 2016 10:42AM EST | DOI: 10.1002/stem.2414

  24. Tissue-Specific Stem Cells

    1. AKT signaling prevailing in mesenchymal stromal cells modulates the functionality of hematopoietic stem cells via intercellular communication

      Shweta Singh, Ranjita Devi Moirangthem, Anuradha Vaidya, Sapana Jalnapurkar, Lalita Limaye and Vaijayanti Kale

      Accepted manuscript online: 14 JUN 2016 10:42AM EST | DOI: 10.1002/stem.2409

  25. Translational and Clinical Research

    1. Cryopreserved MSCs are Susceptible to T-cell Mediated Apoptosis which is partly Rescued by IFNγ Licensing

      Raghavan Chinnadurai, Ian B Copland, Marco A Garcia, Christopher T Petersen, Christopher N Lewis, Edmund K Waller, Allan D Kirk and Jacques Galipeau

      Accepted manuscript online: 14 JUN 2016 10:42AM EST | DOI: 10.1002/stem.2415

  26. Tissue-Specific Stem Cells

    1. You have full text access to this OnlineOpen article
      Vascular Stem/Progenitor Cell Migration Induced by SMC-derived CCL2 and CXCL1 Contributes to Neointima Formation

      Baoqi Yu, Mei Mei Wong, Claire MF Potter, Russell ML Simpson, Eirini Karamariti, Zhongyi Zhang, Lingfang Zeng, Derek Warren, Yanhua Hu, Wen Wang and Qingbo Xu

      Accepted manuscript online: 14 JUN 2016 10:42AM EST | DOI: 10.1002/stem.2410

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      Schematic illustration of the role of CCL2 and CXCL1 released from SMCs in enhancing VPCs chemotaxis. SMCs release CCL2 and CXCL1 into the medium. When VPCs are treated with this SMC conditioned medium, these chemokines bind to their corresponding receptors CCR2 and CXCR2 on the VPCs. The GTPase Rac1 become activated and then p38 is phosphorylated via Rac1, finally leading to increased VPC migration. SMC conditioned medium also induces expression of cytoskeleton related proteins paxillin, vinculin and phosphorylated FAK, which may also activate the Rac1 signaling pathway.

    2. Folate Receptor Alpha Upregulates Oct4, Sox2 and Klf4 and Downregulates miR-138 and miR-let-7 in Cranial Neural Crest Cells

      Vineet Mohanty, Amar Shah, Elise Allender, M Rizwan Siddiqui, Sarah Monick, Shunsuke Ichi, Barbara Mania-Farnell, David G McLone, Tadanori Tomita and Chandra Shekhar Mayanil

      Accepted manuscript online: 14 JUN 2016 10:42AM EST | DOI: 10.1002/stem.2421

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      Hypothetical model of FRα function in NCCs. In response to FA, FRα translocates to the nucleus where it binds the cis-regulatory elements of Oct4, Sox2 and Klf4, activating transcription; this in turn activates downstream targets such as Trim71 and down-regulates levels of miR-138 and miR-let-7, which target Oct4 and Trim71 respectively thus re-moving the inhibitory effects on Oct4 and Trim71 expression.

    3. Loss of Sfrp2 in the Niche Amplifies Stress-Induced Cellular Responses, and Impairs the in Vivo Regeneration of the Hematopoietic Stem Cell Pool

      Franziska Ruf, Christina Schreck, Alina Wagner, Sandra Grziwok, Charlotta Pagel, Sandra Romero, Matthias Kieslinger, Christian Peschel, Katharina S. Götze, Rouzanna Istvanffy and Robert A.J Oostendorp

      Accepted manuscript online: 14 JUN 2016 10:42AM EST | DOI: 10.1002/stem.2416

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      Hematopoietic stress (co-culture, regeneration, genotoxicity, and aging) results in reduced hematopoietic stem cell (HSC) numbers and quality. Here, we show that stromal Sfrp2 dampens the response of HSC to different forms of stress in vitro (co-cultures) and in vivo (regeneration, genotoxic insult, and aging). Without Sfrp2 (right hand figure), the niche's ability to limit the stress response is diminished. As a result, HSC activated from quiescence (qHSC) into an activated state (aHSC) show an amplified stress response with an increased DNA damage response. In this Sfrp2-deficient environment, aHSC do not self-renew efficiently, which results in a defective regeneration of the HSC pool. Thus, Sfrp2 secreted by the niche preserves the number of HSCs, a finding which may help to identify new ways to prevent the loss of stem cells under stress conditions.

  27. Translational and Clinical Research

    1. Clinical Trial of Human Umbilical Cord Blood-derived Stem Cells for the Treatment of Moderate-to-Severe Atopic Dermatitis: Phase I/IIa Studies

      Hyung-Sik Kim, Ji Hyun Lee, Kyoung-Hwan Roh, Hee Jin Jun, Kyung-Sun Kang and Tae-Yoon Kim

      Accepted manuscript online: 3 JUN 2016 12:45AM EST | DOI: 10.1002/stem.2401

  28. Embryonic Stem Cells/Induced Pluripotent Stem Cells

    1. You have free access to this content
      One stone for multiple birds: Generating universally compatible human embryonic stem cells

      Dejin Zheng, Xiaofang Wang and Ren-He Xu

      Accepted manuscript online: 2 JUN 2016 03:31AM EST | DOI: 10.1002/stem.2407

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      Immune cells in a recipient, including dendritic cells, effector T cells etc., recognize and attack foreign cells from a donor via class-I and -II HLAs, while a host's NK cells kill foreign cells without HLAs. Universally compatible (UC) hESCs can be generated via genetic manipulations, e.g., repression or deletion of the heavy chain or light chain (B2M) of HLA-class I and CIITA to abolish immune response, mediated by class-I and -II HLAs, respectively, and via ectopic expression of immunosuppressive molecules such as HLA-G, HLA-E, CTLA4-Ig, and PD-L1 to inhibit NK or T cell-mediated killing. Thus, UC-hESCs and their progeny can escape immune recognition and elimination by the host.

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      Measuring physiological responses of human pluripotent stem cell derived cardiomyocytes to drugs and disease

      Berend J. van Meer, Leon G.J. Tertoolen and Christine L. Mummery

      Accepted manuscript online: 2 JUN 2016 03:30AM EST | DOI: 10.1002/stem.2403

      Thumbnail image of graphical abstract

      Measuring pluripotent stem cell derived cardiomyocyte physiology

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